Engineered Microtissues Formed by Schiff Base Crosslinking Restore the Chondrogenic Potential of Aged Mesenchymal Stem Cells

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Author(s) Millan, Christopher, Cavalli, Emma, Groth, Thomas, Maniura-Weber, Katharina, Zenobi-Wong, Marcy
Publication Type Journal Items, Publication Status: Published
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Title Engineered Microtissues Formed by Schiff Base Crosslinking Restore the Chondrogenic Potential of Aged Mesenchymal Stem Cells
Author(s) Millan, Christopher
Cavalli, Emma
Groth, Thomas
Maniura-Weber, Katharina
Zenobi-Wong, Marcy
Journal or Series Title Advanced Healthcare Materials
Volume Number 4
Issue Number 9
Start Page 1348
End Page 1358
ISSN 2192-2640
2192-2659
Publisher Wiley-VCH
Publication Place Weinheim
Publication Date 2015-06
Keyword(s) Aging
Chondrogenesis
Microtissues
Mesenchymal stem cells
Schiff base
Abstract A universal method for reproducibly directing stem cell differentiation remains a major challenge for clinical applications involving cell-based therapies. The standard approach for chondrogenic induction by micromass pellet culture is highly susceptible to interdonor variability. A novel method for the fabrication of condensation-like engineered microtissues (EMTs) that utilizes hydrophilic polysaccharides to induce cell aggregation is reported here. Chondrogenesis of mesenchymal stem cells (MSCs) in EMTs is significantly enhanced compared to micromass pellets made by centrifugation measured by type II collagen gene expression, dimethylmethylene blue assay, and histology. MSCs from aged donors that fail to differentiate in pellet culture are successfully induced to synthesize cartilage-specific matrix in EMTs under identical media conditions. Furthermore, the EMT polysaccharides support the loading and release of the chondroinduction factor transforming growth factor 3 (TGF-3). TGF--loaded EMTs (EMT+TGF) facilitate cartilaginous tissue formation during culture in media not supplemented with the growth factor. The clinical potential of this approach is demonstrated in an explant defect model where EMT+TGF from aged MSCs synthesize de novo tissue containing sulfated glycosaminoglycans and type II collagen in situ.
DOI 10.1002/adhm.201500102
Additional Notes Received 12 February 2015, Revised 12 March 2015, Article first published online 9 April 2015
Document Type Article
Publication Status Published
Language English
Assigned Organisational Unit(s) 03949
Organisational Unit(s)
NEBIS System Number 007325766
Source Database ID WOS-000356834000010
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@article{Mlln2015,
  author = "Millan, Christopher and Cavalli, Emma and Groth, Thomas and Maniura-Weber, Katharina and Zenobi-Wong, Marcy",
  title = "{E}ngineered {M}icrotissues {F}ormed by {S}chiff {B}ase {C}rosslinking {R}estore the {C}hondrogenic {P}otential of {A}ged {M}esenchymal {S}tem {C}ells",
  journal = "Advanced Healthcare Materials",
  year = 2015,
  volume = "4",
  number = "9",
  pages = "1348--1358",
  month = jun,
}


E-Citations record created: Mon, 20 Jul 2015, 08:44:12 CET